Little is known about the effects of cocaine or heroine on the immune system of injection drug users (IDUs). Furthermore, to our knowledge, no immunologic studies have been conducted to determine the impact of the simultaneous use of these drugs (speedball). This drug mixture could have a significant suppressive effect on the immune response leading to the development of infectious diseases. To study the impact of speedball use on the immune system we will examine immunologic parameters and function in 200 speedball users. The pattern of drug use and general health status will be determined for each individual. The presence of coexistent diseases that may influence the immunologic status of the participants, specifically, HIV,, hepatitis B and hepatitis C infections will be determined. Delayed hypersensitivity response, frequency of circulating lymphocyte populations and serum cytokine concentration will be examined. Antigen panel for skin tests will include tetanus, candida, mumps and tuberculin. The frequency of peripheral blood T cells, CD4+ T cells, CD8+ T cells, B lymphocytes, natural killer cells, activated T cells (CD8+/HLA-DR+ and CD8+/CD38+) will be assessed by flow cytometry. IL-1 beta, IL-2, users, immunologic functional studies will be performed. The proliferative response, cytokine secretion and expansion of lymphocytic populations of peripheral blood mononuclear cells (PBMC) will be evaluated after stimulation with a poly-antigenic immunomodulator and a mitogenic stimuli. Results of immunologic tests of speedball users will be compared with studies performed in healthy individuals. The proposed research could provide new insights in the immunomodulating effects of heroin and cocaine in IDUs. Also, this project could lead to the development of therapeutic strategies that may improve the immune status of speedball users.